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1.  Airway reactions and emergence times in general laryngeal mask airway anaesthesia 
Desflurane's short emergence time supports fast track anaesthesia. Data on the rate of upper airway complications and emergence time when desflurane is used with laryngeal mask airway (LMA) are controversial and limited.
To compare recovery time variables and the rates of upper airway adverse events in patients with an LMA undergoing general surgery with desflurane, sevoflurane, isoflurane or propofol anaesthesia.
A systematic review and meta-analysis of randomised controlled trials (RCTs).
A systematic search for eligible RCTs in Embase (Elsevier) and in PubMed (National Library of Medicine) databases up to September 2013.
RCTs investigating the rates of cough overall, cough at emergence, laryngospasm, time to eye opening, time to removal of the LMA, time to respond to command and time to state date of birth in patients with an LMA, during emergence from desflurane, sevoflurane, isoflurane or propofol anaesthesia.
Thirteen RCTs were included and analysed. We found a strong interstudy variability. There was no difference in the rates of upper airway events between desflurane and sevoflurane or between desflurane and a control group consisting of all the other anaesthetics combined. Comparing desflurane (n = 284) with all other anaesthetic groups (n = 313), the risk ratio [95% confidence interval (95% CI)] was 1.12 (0.63 to 2.02, P = 0.70). Cough at emergence was only measured in patients receiving desflurane (n = 148) and sevoflurane (n = 146): the risk ratio (95% CI) was 1.49 (0.55 to 4.02, P = 0.43). Laryngospasm was rare and there was no significant difference in its incidence when desflurane (n = 262) was compared with all other anaesthetics combined (n = 289; risk ratio 1.03; 95% CI 0.33 to 3.20, P = 0.96). The times of all emergence variables were significantly faster in the desflurane group than in all other groups.
When using an LMA, upper airway adverse reactions in association with desflurane anaesthesia were no different from those noted with sevoflurane, isoflurane or propofol anaesthesia. Emergence from general anaesthesia with desflurane is significantly faster than all the other anaesthetics. Due to interstudy variations and the small size of the trials, further large-scale, multicentre studies are required to confirm or refute the results of this meta-analysis.
PMCID: PMC4276573  PMID: 25545286
2.  Safety and feasibility of xenon as an adjuvant to sevoflurane anaesthesia in children undergoing interventional or diagnostic cardiac catheterization: study protocol for a randomised controlled trial 
Trials  2015;16:74.
Xenon has minimal haemodynamic side effects when compared to volatile or intravenous anaesthetics. Moreover, in in vitro and in animal experiments, xenon has been demonstrated to convey cardio- and neuroprotective effects. Neuroprotection could be advantageous in paediatric anaesthesia as there is growing concern, based on both laboratory studies and retrospective human clinical studies, that anaesthetics may trigger an injury in the developing brain, resulting in long-lasting neurodevelopmental consequences. Furthermore, xenon-mediated neuroprotection could help to prevent emergence delirium/agitation. Altogether, the beneficial haemodynamic profile combined with its putative organ-protective properties could render xenon an attractive option for anaesthesia of children undergoing cardiac catheterization.
In a phase-II, mono-centre, prospective, single-blind, randomised, controlled study, we will test the hypothesis that the administration of 50% xenon as an adjuvant to general anaesthesia with sevoflurane in children undergoing elective cardiac catheterization is safe and feasible. Secondary aims include the evaluation of haemodynamic parameters during and after the procedure, emergence characteristics, and the analysis of peri-operative neuro-cognitive function.
A total of 40 children ages 4 to 12 years will be recruited and randomised into two study groups, receiving either a combination of sevoflurane and xenon or sevoflurane alone.
Children undergoing diagnostic or interventional cardiac catheterization are a vulnerable patient population, one particularly at risk for intra-procedural haemodynamic instability. Xenon provides remarkable haemodynamic stability and potentially has cardio- and neuroprotective properties. Unfortunately, evidence is scarce on the use of xenon in the paediatric population. Our pilot study will therefore deliver important data required for prospective future clinical trials.
Trial registration
EudraCT: 2014-002510-23 (5 September 2014)
PMCID: PMC4350978  PMID: 25886748
Anaesthetics; Inhalation; Xenon; Sevoflurane; Congenital heart defects; Cardiac catheterization
3.  Design and methodology of SNAP-1: a Sprint National Anaesthesia Project to measure patient reported outcome after anaesthesia 
Patient satisfaction is an important metric of health-care quality. Accidental awareness under general anaesthesia (AAGA) is a serious complication of anaesthesia care which may go unrecognised in the immediate perioperative period but leads to long-term psychological harm for affected patients. The SNAP-1 study aimed to measure patient satisfaction with anaesthesia care and the incidence of AAGA, reported on direct questioning within 24 h of surgery, in a large multicentre cohort. A secondary aim of SNAP-1 was to test the effectiveness of a new network of Quality Audit and Research Coordinators in NHS anaesthetic departments, to achieve widespread study participation and high patient recruitment rates. This manuscript describes the study methodology.
SNAP-1 was a prospective observational cohort study. The study protocol was approved by the National Research Ethics Service. All UK NHS hospitals with anaesthetic departments were invited to participate. Adult patients undergoing any type of non-obstetric surgery were recruited in participating hospitals on 13th and 14th May 2014. Demographic data were collected by anaesthetists providing perioperative care. Patients were then approached within 24 h of surgery to complete two questionnaires—the Bauer patient satisfaction questionnaire (to measure patient reported outcome) and the modified Brice questionnaire (to detect possible accidental awareness). Completion of postoperative questionnaires was taken as evidence of implied consent. Results were recorded on a standard patient case report form, and local investigators entered anonymised data into an electronic database for later analysis by the core research team.
Preliminary analyses indicate that over 15,000 patients were recruited across the UK, making SNAP-1 the largest NIHR portfolio-adopted study in anaesthesia to date. Both descriptive and analytic epidemiological analyses will be used to answer specific questions about the patient perception of anaesthesia care overall and in surgical sub-specialties and to determine the incidence of AAGA.
The SNAP-1 study recruited a large number of UK hospitals and thousands of perioperative patients using newly established networks in the UK anaesthetic profession. The results will provide benchmarking information to aid interpretation of patient satisfaction data and also determine the incidence of AAGA reported on a single postoperative visit.
Electronic supplementary material
The online version of this article (doi:10.1186/s13741-015-0011-2) contains supplementary material, which is available to authorized users.
PMCID: PMC4422533  PMID: 25949810
Patient-reported outcome; Patient satisfaction; Anesthesia awareness; Epidemiology; Cohort study
4.  The Effects of Local Anaesthetics on QT Parameters during Thoracic Epidural Anaesthesia Combined with General Anaesthesia: Ropivacaine versus Bupivacaine 
Balkan medical journal  2013;30(4):410-414.
Many studies focusing on the effects of local anaesthetics on QT intervals have been performed, but the articles evaluating the relationship between thoracic epidural anaesthesia combined with general anaesthesia and QT parameters are very limited.
We aimed to compare the effects of bupivacaine and ropivacaine on QT interval, corrected QT, dispersion of QT, and corrected dispersion of QT in patients undergoing lung resection under thoracic epidural anaesthesia combined with general anaesthesia.
Study Design:
Prospective clinical study.
Thirty ASA physical status 1–3 patients requiring thoracic epidural anaesthesia combined with general anaesthesia for thoracic surgery. Patients were randomly assigned to two groups, which were allocated to receive either bupivacaine (Group B) or ropivacaine (Group R) during thoracic epidural anaesthesia. Following haemodynamic monitoring, a thoracic epidural catheter was inserted. Local anaesthetic at an average dose of 1.5 mL/ segment was given through an epidural catheter. The same general anaesthesia protocol was administered in both groups. Records and measurements were performed on 10 phases that were between the thoracic epidural catheter insertion to the 5th min of endobronchial intubation. In all phases, systolic arterial pressure, diastolic arterial pressure, mean arterial pressure, heart rate, peripheral O2 saturation, and electrocardiogram monitoring were performed in patients. All QT parameters were recorded by 12-lead electrocardiogram and analysed manually by a cardiologist.
QT intervals were similar between two groups. In Group R, corrected QT values at the 20th min of local anaesthetic injection and the 5th min of endobronchial intubation were shorter than those in Group B (p<0.05). The basal dispersion of QT and dispersion of QT values at the 1st min of propofol injection were shorter than those in Group R (p<0.05). The corrected dispersion of QT value at the 1st min of propofol injection was shorter in Group R (p<0.05). In Group R, the decrease in mean arterial pressure at the 1st min of fentanyl injection was significant compared with Group B (p<0.05). There was no significant difference between the groups with respect to heart rate and complications.
The corrected QT, dispersion of QT, and corrected dispersion of QT intervals were slightly longer in the patients receiving bupivacaine compared with those receiving ropivacaine in various phases of the present study.
PMCID: PMC4115939  PMID: 25207150
Bupivacaine; ropivacaine; QT parameters; thoracic epidural anaesthesia; local anaesthetics
5.  Early postoperative cognitive dysfunction and postoperative delirium after anaesthesia with various hypnotics: study protocol for a randomised controlled trial - The PINOCCHIO trial 
Trials  2011;12:170.
Postoperative delirium can result in increased postoperative morbidity and mortality, major demand for postoperative care and higher hospital costs. Hypnotics serve to induce and maintain anaesthesia and to abolish patients' consciousness. Their persisting clinical action can delay postoperative cognitive recovery and favour postoperative delirium. Some evidence suggests that these unwanted effects vary according to each hypnotic's specific pharmacodynamic and pharmacokinetic characteristics and its interaction with the individual patient.
We designed this study to evaluate postoperative delirium rate after general anaesthesia with various hypnotics in patients undergoing surgical procedures other than cardiac or brain surgery. We also aimed to test whether delayed postoperative cognitive recovery increases the risk of postoperative delirium.
After local ethics committee approval, enrolled patients will be randomly assigned to one of three treatment groups. In all patients anaesthesia will be induced with propofol and fentanyl, and maintained with the anaesthetics desflurane, or sevoflurane, or propofol and the analgesic opioid fentanyl.
The onset of postoperative delirium will be monitored with the Nursing Delirium Scale every three hours up to 72 hours post anaesthesia. Cognitive function will be evaluated with two cognitive test batteries (the Short Memory Orientation Memory Concentration Test and the Rancho Los Amigos Scale) preoperatively, at baseline, and postoperatively at 20, 40 and 60 min after extubation.
Statistical analysis will investigate differences in the hypnotics used to maintain anaesthesia and the odds ratios for postoperative delirium, the relation of early postoperative cognitive recovery and postoperative delirium rate. A subgroup analysis will be used to categorize patients according to demographic variables relevant to the risk of postoperative delirium (age, sex, body weight) and to the preoperative score index for delirium.
The results of this comparative anaesthesiological trial should whether each the three hypnotics tested is related to a significantly different postoperative delirium rate. This information could ultimately allow us to select the most appropriate hypnotic to maintain anaesthesia for specific subgroups of patients and especially for those at high risk of postoperative delirium.
Registered at Number NCT00507195
PMCID: PMC3155116  PMID: 21733178
6.  Inguinal Hernia Repair: Local or General Anaesthesia? 
Specialist hernia centres and public hospitals with a dedicated hernia service (Plymouth Hernia Service) have achieved remarkable results for inguinal hernia repair with the use of local anaesthesia and set the standards for groin hernia surgery. There is minimal data in the literature as to whether such results are reproducible in the National Health Service in the UK.
A retrospective analysis of all inguinal hernia repairs performed in one district general hospital over a 9-year period was performed. The outcome measures were type of anaesthesia used, early and late postoperative complications and recurrence. A postal questionnaire survey was conducted to obtain satisfaction rates. In addition, a postal questionnaire survey of consultant surgeons in Wales was performed to determine the use of local anaesthesia and day-case rates for inguinal hernia repair.
A total of 577 hernia repairs were performed during the study period. Of these, 369 (64%) repairs were performed under local anaesthesia (LA) and 208 (36%) under general anaesthesia (GA). Day-case repair was achieved in 70% (400) of cases. The day-case rates were significantly higher under LA compared to GA (82.6% versus 42.6%; P < 0.05). Patients operated under LA had lower postoperative analgesic requirements and lower incidence of urinary retention compared with the GA group (P < 0.05). There were 7 (1.2%) recurrences at a median follow-up of 5.1 years (range, 10.3–2.5 years). Postal questionnaire revealed higher satisfaction rates with LA compared to GA repair. Only 15% of surgeons in Wales offer the majority of their patients local anaesthetic repair.
The use of LA results in increased day-case rates, lesser postoperative analgesic requirements and fewer micturition problems. The excellent results obtained by specialist hernia centres can be reproduced by district general hospitals by increasing the use of LA to repair inguinal hernias.
PMCID: PMC2048598  PMID: 17688723
Inguinal hernia; Local anaesthesia; District general hospital
7.  Peak and averaged bicoherence for different EEG patterns during general anaesthesia 
Changes in nonlinear neuronal mechanisms of EEG generation in the course of general anaesthesia have been extensively investigated in research literature. A number of EEG signal properties capable of tracking these changes have been reported and employed in anaesthetic depth monitors. The degree of phase coupling between different spectral components is a marker of nonlinear EEG generators and is claimed to be an important aspect of BIS. While bicoherence is the most direct measure of phase coupling, according to published research it is not directly used in the calculation of BIS, and only limited studies of its association with anaesthetic depth and level of consciousness have been published. This paper investigates bicoherence parameters across equal band and unequal band bifrequency regions, during different states of anaesthetic depth relating to routine clinical anaesthesia, as determined by visual inspection of EEG.
41 subjects scheduled for day surgery under general anaesthesia were recruited into this study. EEG bicoherence was analysed using average and smoothed-peak estimates calculated over different regions on the bifrequency plane. Statistical analysis of associations between anaesthetic depth/state of consciousness and bicoherence estimates included linear regression using generalised linear mixed effects models (GLMs), ROC curves and prediction probability (Pk).
Bicoherence estimates for the δ_θ region on the bifrequency plane were more sensitive to anaesthetic depth changes compared to other bifrequency regions. Smoothed-peak bicoherence displayed stronger associations than average bicoherence. Excluding burst suppression and large transients, the δ_θ peak bicoherence was significantly associated with level of anaesthetic depth (z = 25.74, p < 0.001 and R2 = 0.191). Estimates of Pk for this parameter were 0.889(0.867-0.911) and 0.709(0.689-0.729) respectively for conscious states and anaesthetic depth levels (comparable BIS estimates were 0.928(0.905-0.950) and 0.801(0.786-0.816)). Estimates of linear regression and areas under ROC curves supported Pk findings. Bicoherence for eye movement artifacts were the most distinctive with respect to other EEG patterns (average |z| value 13.233).
This study quantified associations between deepening anaesthesia and increase in bicoherence for different frequency components and bicoherence estimates. Increase in bicoherence was also established for eye movement artifacts. While identified associations extend earlier findings of bicoherence changes with increases in anaesthetic drug concentration, results indicate that the unequal band bifrequency region, δ_θ, provides better predictive capabilities than equal band bifrequency regions.
PMCID: PMC2998515  PMID: 21092128
8.  Noxious stimulation in children receiving general anaesthesia evokes an increase in delta frequency brain activity 
Pain  2014;155(11):2368-2376.
Clinically required noxious cannulation performed in children receiving sevoflurane monoanaesthesia causes a change in electrophysiological brain activity.
More than 235,000 children/year in the UK receive general anaesthesia, but it is unknown whether nociceptive stimuli alter cortical brain activity in anaesthetised children. Time-locked electroencephalogram (EEG) responses to experimental tactile stimuli, experimental noxious stimuli, and clinically required cannulation were examined in 51 children (ages 1–12 years) under sevoflurane monoanaesthesia. Based on a pilot study (n = 12), we hypothesised that noxious stimulation in children receiving sevoflurane monoanaesthesia would evoke an increase in delta activity. This was tested in an independent sample of children (n = 39), where a subset (n = 11) had topical local anaesthetic applied prior to stimulation. A novel method of time-locking the stimuli to the EEG recording was developed using an event detection interface and high-speed camera. Clinical cannulation evoked a significant increase (34.2 ± 8.3%) in delta activity (P = 0.042), without concomitant changes in heart rate or reflex withdrawal, which was not observed when local anaesthetic was applied (P = 0.30). Experimental tactile (P = 0.012) and noxious (P = 0.0099) stimulation also evoked significant increases in delta activity, but the magnitude of the response was graded with stimulus intensity, with the greatest increase evoked by cannulation. We demonstrate that experimental and clinically essential noxious procedures, undertaken in anaesthetised children, alter the pattern of EEG activity, that this response can be inhibited by local anaesthetic, and that this measure is more sensitive than other physiological indicators of nociception. This technique provides the possibility that sensitivity to noxious stimuli during anaesthesia could be investigated in other clinical populations.
PMCID: PMC4247379  PMID: 25218826
EEG; Anaesthetics; Paediatrics
9.  Incidence of Epileptiform EEG Activity in Children during Mask Induction of Anaesthesia with Brief Administration of 8% Sevoflurane 
PLoS ONE  2012;7(7):e40903.
A high incidence of epileptiform activity in the electroencephalogram (EEG) was reported in children undergoing mask induction of anaesthesia with administration of high doses of sevoflurane for 5 minutes and longer. This study was performed to investigate whether reducing the time of exposure to a high inhaled sevoflurane concentration would affect the incidence of epileptiform EEG activity. It was hypothesized that no epileptiform activity would occur, when the inhaled sevoflurane concentration would be reduced from 8% to 4% immediately after the loss of consciousness.
Methodology/Principal Findings
70 children (age 7–96 months, ASA I–II, premedication with midazolam) were anaesthetized with 8% sevoflurane in 100% oxygen via face mask. Immediately after loss of consciousness, the sevoflurane concentration was reduced to 4%. EEGs were recorded continuously and were later analyzed visually with regard to epileptiform EEG patterns. Sevoflurane at a concentration of 8% was given for 1.2±0.4 min (mean ± SD). In 14 children (20%) epileptiform EEG patterns without motor manifestations were observed (delta with spikes (DSP), rhythmic polyspikes (PSR), epileptiform discharges (PED) in 10, 10, 4 children (14%, 14%, 6%)). 38 children (54%) had slow, rhythmic delta waves with high amplitudes (DS) appearing on average before DSP.
The hypothesis that no epileptiform potentials would occur during induction of anaesthesia with a reduction of the inspired sevoflurane concentration from 8% to 4% directly after LOC was not proved. Even if 8% sevoflurane is administered only briefly for induction of anaesthesia, epileptiform EEG activity may be observed in children despite premedication with midazolam.
PMCID: PMC3400655  PMID: 22829896
10.  Comparison of sodium diclofenac, ketamine and propofol with fentanyl and midazolam in balanced anaesthesia 
Analgesia is based on balanced anaesthesia, which is usually maintained by administration of narcotic agents. In some patients, it is not possible to use narcotics. We compared hemodynamic changes, anaesthesia depth, emetic sequelae and post-operative pain between sodium Diclofenac, Ketamine-Propofol (DKP) and Fentanyl-Midazolam (FM).
The effectiveness of an anaesthetic technique employing sodium was compared against in patients undergoing elective surgery.
Settings and Design:
In a clinical trial study, 82 patients who attended for an elective surgery were randomly divided into two groups.
Materials and Methods:
In DKP group pre-medication included Sodium Diclofenac 1 mg/kg and Midazolam 0.02 mg/kg, whereas, in FM group they were Fentanyl 2 μg/kg and Midazolam 0.02 mg/ kg. Anaesthesia induction in both groups was the same. Anaesthesia was conserved in DKP group by using Propofol plus Ketamine infusion plus N2O 50% and in FM group with Fentanyl plus Midazolam plus N2O 50%. Hemodynamic changes, depth of anaesthesia, nausea and vomiting, post operative analgesic effects were recorded.
Hemodynamic changes and depth of anaesthesia were similar throughout the maintenance phase in two groups. In FM group, significant increase in heart rate was recorded in recovery room. Pain score according to visual analogue scale (VAS) and need for analgesics, was significantly more in FM group compared to DKP group (P = 0.000). No patient suffered from nausea, vomiting or hallucinations.
This study revealed that intravenous administration of Sodium Diclofenac along with Ketamine and Propofolplus N2O 50% for general anaesthesia provides a balanced anaesthesia as well as hemodynamic stability, and adequate depth of anaesthesia. It also reduces the postoperative pain and need for narcotics. We recommended DKP plus N2O 50% method for patients prohibited from opioid administration. It will be an acceptable method in sensitive patients.
PMCID: PMC4173415  PMID: 25885384
Balanced anaesthesia; ketamine; propofol; sodium diclofenac
11.  General anaesthesia or conscious sedation for painful procedures in childhood cancer: the family‘s perspective 
Archives of Disease in Childhood  2003;88(3):253-257.
Background: Until recently, midazolam sedation was routinely used in our institution for bone marrow aspirates and lumbar punctures in children with cancer. It has been perceived by many doctors and nurses as being well tolerated by children and their families.
Aim: To compare the efficacy of inhalational general anaesthesia and midazolam sedation for these procedures.
Methods: A total of 96 children with neoplastic disorders, who received either inhalational general anaesthesia with sevoflurane, nitrous oxide, and oxygen (GA) or sedation with oral or nasal midazolam (SED) as part of their routine preparation for procedures were studied. The experiences of these childen were examined during their current procedure and during their first ever procedure. Main outcome measures were the degree of physical restraint used on the child, and the levels of distress and pain experienced by the child during the current procedure and during the first procedure. The family‘s preference for future procedures was also determined.
Results: During 102 procedures under GA, restraint was needed on four occasions (4%) when the anaesthetic mask was first applied, minimal pain was reported, and children were reported as distressed about 25% of the time. During 80 SED procedures, restraint was required in 94%, firm restraint was required in 66%, the child could not be restrained in 14%, median pain score was 6 (scale 0 (no pain) to 6 (maximum pain)), and 90% of the parents reported distress in their child. Ninety per cent of families wanted GA for future procedures. Many families reported dissatisfaction with the sedation regime and raised concerns about the restraint used on their child.
Conclusions: This general anaesthetic regime minimised the need for restraint and was associated with low levels of pain and distress. The sedation regime, by contrast, was much less effective. There was a significant disparity between the perceptions of health professionals and those of families with respect to how children coped with painful procedures.
PMCID: PMC1719477  PMID: 12598395
12.  Propofol or sevoflurane anaesthesia does not affect hepatic integrity as assessed by the M30 & M65 cell death markers & liver enzymes 
Background & objectives:
General anaesthetics may induce apoptosis. The pro-apoptotic/necrotic markers M30 (caspase-cleaved cytokeratin-18) and M65 (intact cytokeratin-18) have been used to identify early apoptosis in liver disease. The aim of this study was to detect the effect of propofol and sevoflurane anaesthesia on these markers and blood transaminase levels in female patients undergoing elective surgery.
Sixty-seven women undergoing mastectomy or thyroidectomy under general anaesthesia were randomly allocated to the propofol or sevoflurane groups. Venous blood samples for measuring the apoptotic and necrotic markers M30 and M65 as well as for measuring the alanine aminotransferase (ALT) and the aspartate aminotransferase (AST) liver enzymes were collected before induction of anaesthesia, immediately after completion of surgery, and 24 and 48 h postoperatively.
The M30 values preoperatively and 0, 24 and 48 h postoperatively were 280±229, 300±244, 267±198 and 254±189 U/l in the propofol group and 237±95, 242±109, 231±94 and 234±127 U/l in the sevoflurane group, respectively. The M30 values did not differ within or between the groups. The M65 levels at the same time intervals were 470±262, 478±271, 456±339 and 485±273 in the propofol group and 427±226, 481±227, 389±158 and 404±144 U/l in the sevoflurane group, respectively. No significant changes were found in the M65 either within or between the propofol and the sevoflurane groups. The ALT and AST levels did not change at these time intervals.
Interpretation & conclusions:
Under the present study design propofol or sevoflurane anaesthesia did not induce apoptosis or affected the liver function as assessed by the M30, M65 markers and liver enzymes in patients undergoing mastectomy or thyroidectomy under general anaesthesia.
PMCID: PMC4311316  PMID: 25579144
Anaesthesia; apoptosis; liver; M30; M65; necrotic markers; propofol; sevoflurane
13.  Does regional compared to local anaesthesia influence outcome after arteriovenous fistula creation? 
Trials  2013;14:263.
An arteriovenous fistula is the optimal form of vascular access in patients with end-stage renal failure requiring haemodialysis. Unfortunately, approximately one-third of fistulae fail at an early stage. Different anaesthetic techniques can influence factors associated with fistula success, such as intraoperative blood flow and venous diameter. A regional anaesthetic brachial plexus block results in vasodilatation and improved short- and long-term fistula flow compared to the infiltration of local anaesthetic alone. This, however, has not yet been shown in a large trial to influence long-term fistula patency, the ultimate clinical measure of success.
The aim of this study is to compare whether a regional anaesthetic block, compared to local anaesthetic infiltration, can improve long-term fistula patency.
This study is an observer-blinded, randomised controlled trial. Patients scheduled to undergo creation of either brachial or radial arteriovenous fistulae will receive a study information sheet, and consent will be obtained in keeping with the Declaration of Helsinki. Patients will be randomised to receive either: (i) an ultrasound guided brachial plexus block using lignocaine with adrenaline and levobupivicaine, or (ii) local anaesthetic infiltration with lignocaine and levobupivicaine.
A total of 126 patients will be recruited. The primary outcome is fistula primary patency at three months. Secondary outcomes include primary patency at 1 and 12 months, secondary patency and fistula flow at 1, 3 and 12 months, flow on first haemodialysis, procedural pain, patient satisfaction, change in cephalic vein diameter pre- and post-anaesthetic, change in radial or brachial artery flow pre- and post-anaesthetic, alteration of the surgical plan after anaesthesia as guided by vascular mapping with ultrasound, and fistula infection requiring antibiotics.
No large randomised controlled trial has examined the influence of brachial plexus block compared with local anaesthetic infiltration on the long-term patency of arteriovenous fistulae. If the performance of brachial plexus block increases fistulae patency, this will have significant clinical and financial benefits as the number of patients able to commence haemodialysis when planned should increase, and the number of “redo” or revision procedures should be reduced.
Trial registration
This study has been approved by the West of Scotland Research Ethics Committee 5 (reference no. 12/WS/0199) and is registered with the database (reference no. NCT01706354).
PMCID: PMC3765116  PMID: 23958289
Fistula; Patency; Flow; Anaesthetic; Local; Nerve block; Renal failure
14.  The assessment of bupivacaine-tramadol and levobupivacaine-tramadol combinations for preemptive caudal anaesthesia in children: a randomized, double-blind, prospective study 
Caudal block is the regional anesthetic technique that is used most frequently in pediatric surgery and bupivacaine and levobupivacaine are widely utilized in this technique. Opioid drugs have been added to local anesthetic solutions to prolong duration of analgesia but ideal combination were not found. We compared the postoperative analgesic efficacy of equal concentrations of bupivacaine or levobupivacaine plus tramadol in pediatric patients. Sixty eight children aged 2 to 7 years who were undergoing inguinal herniorrhaphies or orchidopexies received bupivacaine 0.25% plus tramadol 2 mg/kg (1 ml/kg) (BT group) or levobupivacaine 0.25% plus tramadol 2 mg/kg (1 ml/kg) (LT group) by the caudal route after laryngeal mask anesthesia. The primary outcome of the study was to compare the duration and quality of postoperative analgesia. The postoperative pain relief was evaluated by the Children and Infants Postoperative Pain Scale (CHIPPS) at 2, 4, 6, 12, and 24 h postoperatively. In addition, the time of first analgesic requirement was noted. The CHIPPS scores were not statistically different between the groups. The duration of analgesia and requirements for rescue analgesia was similar. Urinary retention was observed more often in the BT group. There were no significant differences between groups for arterial pressures and heart rate values after caudal block and during the operation. Caudal bupivacaine plus tramadol and levobupivacaine plus tramadol have similar postoperative analgesic efficacy. But the use of bupivacaine plus tramadol may cause a greater frequency of urinary retention.
PMCID: PMC4073762  PMID: 24995101
Bupivacaine; levobupivacaine; tramadol; anaesthesia; caudal
15.  Caudal anaesthesia for postoperative pain relief in children: a comparative trial of different regimens using plain bupivacaine. 
A comparative trial between three different dosage regimens of bupivacaine administered by the caudal route, used for the prevention of postoperative pain in children undergoing elective inguinal herniotomy or ligation of patient processus vaginalis was undertaken. The regimens compared were bupivacaine 0.25% (1 ml/kg), bupivacaine 0.25% or 0.5%: (Age (years +2)/10 ml per dermatome to be blocked. This being calculated for inguinal surgery to be Age (years) + 2 ml. A linear analogue pain scale was used to evaluate pain, all three regimens being found to produce excellent analgesia, there being no significant difference between the pain scores of the three groups. Time to onset of analgesia, as indicated by changes in intraoperative heart rate in response to surgical stimulation were also similar in all groups. No evidence of postoperative motor weakness or disturbance of bladder function was found and there were no symptoms or signs attributable to local anaesthetic toxicity.
PMCID: PMC2498969  PMID: 2672989
16.  Improving access to preparatory information for children undergoing general anaesthesia for tooth extraction and their families: study protocol for a Phase III randomized controlled trial 
Trials  2014;15:219.
Children can find anaesthesia induction especially distressing and postoperative psychological and physical morbidity are common. Preparation programmes for general anaesthesia (GA) are highly effective in reducing this distress. A Phase II study has already verified the effectiveness of a prototype preoperative GA-coping computer game to help children cope with induction in a dental GA setting. The biggest patient users of pediatric GA services in the UK are children who need to have teeth removed (estimated to be 100,000 yearly). Tooth decay is the most common disease in children worldwide. This study is a Phase III randomized controlled trial (RCT) and will evaluate the effectiveness of the new internet version of this game.
The Phase III RCT will use a double-blind three-armed design. The clinical trial will recruit up to 210 children and will compare the web-based game against standard care and another non-medical game. At least 53 patients in each group will be required for 90% statistical power. Distress will be assessed through an evaluation of the child’s behaviour during the visit and later parental reports of physical and psychological morbidity. The satisfaction of parents and children will be measured; the mode of usage of the web-based game will be automatically recorded and the impact on the service (for example, recovery time and throughput) will be reported.
The Phase III study primary outcome will measure: (1) patient experience: acceptance of anaesthetic induction, child cooperation and distress, reduction of peri- and postoperative morbidity, child and family satisfaction, and (2) service improvement: anaesthetic time and improvement in throughput. Measures will be administered at baseline, at the time of the GA treatment visit, and at 48 hours and one week postoperatively.
This study aims to determine the effectiveness of an online GA-coping game for children and families undergoing tooth extraction under GA.
Trial registration
ISRCTN18265148 (registered 24 November 2013).
PMCID: PMC4229849  PMID: 24919430
General anaesthesia; Children; Preparatory information; Coping; Cognitive behavioural therapy; Role modelling; Early childhood caries; Dental anxiety; Randomized controlled trial (RCT)
17.  General anaesthesia does not contribute to long-term post-operative cognitive dysfunction in adults: A meta-analysis 
Indian Journal of Anaesthesia  2011;55(4):358-363.
The contribution of anaesthesia itself to post-operative cognitive dysfunction (POCD) or the potential protective effect of one specific type of anaesthesia on the occurrence of POCD is unclear.
This is a meta-analysis evaluating the effects of the anaesthetic technique (regional vs. general anaesthesia) on POCD of patients undergoing non-cardiac surgery.
Settings and Design:
Meta-analysis performed in a University affiliated hospital.
A search for randomized controlled trials (RCT) comparing regional anaesthesia to general anaesthesia for surgery was done in PUBMED, MEDLINE, EMBASE, EBM Reviews-Cochrane Central Register of Controlled Trials, PsychINFO and Current Contents/all editions in 2009.
Statistical Analysis:
Data were analyzed with comprehensive Meta-analysis Version 2.2.044.
Twenty-six RCTs including 2365 patients: 1169 for regional anaesthesia and 1196 for general anaesthesia were retained. The standardized difference in means for the tests included in the 26 RCTs was -0.08 (95% confidence interval: –0.17–0.01; P value 0.094; I-squared = 0.00%). The assessor was blinded to the anaesthetic technique for 12 of the RCTs including only 798 patients: 393 for regional anaesthesia and 405 for general anaesthesia. The standardized difference in means for these 12 studies is 0.05 (–0.10–0.20; P=0.51; I-squared = 0.00%).
The present meta-analysis does not support the concerns that a single exposure to general anaesthesia in an adult would significantly contribute to permanent POCD after non-cardiac surgery.
PMCID: PMC3190509  PMID: 22013251
Meta-analysis; post-operative cognitive dysfunction; regional anaesthesia
18.  The impact of age on bispectral index values and EEG bispectrum during anaesthesia with desflurane and halothane in children 
British Journal of Anaesthesia  2006;96(4):480-485.
The relationship between end-tidal sevoflurane concentration, BIS and the EEG bispectrum in children appears dependent on age. The aim of this study was to quantify the BIS values at 1 MAC for desflurane and halothane, and explore the relationship with age for these anaesthetic agents in children.
ECG, EEG and BIS were recorded continuously during the anaesthesia of ninety children aged 6–170 months requiring elective surgery. Fifty children were anaesthetised with desflurane, and forty children with halothane. Recordings were performed through to a steady state of 2 MAC, and thereafter at 1 MAC and 0.5 MAC respectively. The bispectrum of the EEG was estimated using MATLAB© software. For analysis, a multiple correspondence analysis (MCA) was used.
At the steady state of 1 MAC, BIS values were significantly higher with halothane 62 (43–80) compared to desflurane 34 (18–64). BIS values were significantly correlated to age in both groups: DES (r2=0.57; p<0.01) and HALO (r2=0.48; p<0.01). Changes in position in the structured model of the MCA (dependent on the pattern of the EEG bispectrum) were different for the two volatile anaesthetic agents.
BIS values are linked to age of children irrespective of the volatile anaesthetic agent used. In children, the difference in BIS values for different agents at the same MAC can be explained by the specific effect on the EEG bispectrum induced by each anaesthetic agent, bringing into question the ability of the EEG bispectrum to accurately determine depth of anaesthesia in children.
PMCID: PMC2034405  PMID: 16500950
Adolescent; Age Factors; Anesthetics, Inhalation; pharmacology; Body Weight; physiology; Child; Child, Preschool; Electrocardiography; drug effects; Electroencephalography; drug effects; Female; Halothane; pharmacology; Humans; Infant; Isoflurane; analogs & derivatives; pharmacology; Male; Monitoring, Intraoperative; methods; Depth of Anesthesia; EEG; Bispectrum; PCA; Factorial Analysis; Classification; Anesthesia; BIS; Monitoring
19.  Determining entropy values equivalent to the bispectral index values during sevoflurane anaesthesia 
We aimed to identify the entropy levels that would be equivalent to the bispectral index (BIS) levels in sevoflurane anaesthesia in patients who are to undergo elective lumbar disc surgery.
Material and methods
Thirty cases in ASA groups I-II who underwent lumbar disc surgery under general anaesthesia were included in our study after obtaining the consent of the patients and Ethics Committee of our medical school between January 1, 2005 and October 30, 2006. BIS and entropy electrodes were applied at the same time in 30 cases in the study group. The depth of the anaesthesia was regulated so that 10 min after beginning the general anaesthesia the BIS values were between 40 and 60. At the same time equivalent entropy values corresponding to BIS values were obtained.
At the end of the study, entropy values corresponding to general anaesthesia BIS values were identified. General anaesthesia BIS and RE/SE values at 10 min were lower than the values of the control, which was statistically significant (p < 0.05). Equivalent entropy values were obtained lower than the BIS values during general anaesthesia and these values were found to be statistically significant (p < 0.05). The blood pressure (BP) values obtained were very low at equivalent BIS values and when these BP values were compared with the initial BP values they were found to be statistically significant (p < 0.05).
Based on this observation, we think that general anaesthetic agents that might cause severe hypotension could be more safely administered under entropy monitoring.
PMCID: PMC3282514  PMID: 22371773
general anaesthesia; bispectral index; entropy
20.  Pain and Efficacy Rating of a Microprocessor-Controlled Metered Injection System for Local Anaesthesia in Minor Hand Surgery 
Pain Research and Treatment  2011;2011:362396.
Purpose. Little attention has been given to syringe design and local anaesthetic administration methods. A microprocessor-controlled anaesthetic delivery device has become available that may minimize discomfort during injection. The purpose of this study was to document the pain experience associated with the use of this system and to compare it with use of a conventional syringe. Methods. A prospective, randomized clinical trial was designed. 40 patients undergoing carpal tunnel release were block randomized according to sex into a two groups: a traditional syringe group and a microprocessor-controlled device group. The primary outcome measure was surgical pain and local anaesthetic administration pain. Secondary outcomes included volume of anaesthetic used and injection time. Results. Analysis showed that equivalent anaesthesia was achieved in the microprocessor-controlled group despite using a significantly lower volume of local anaesthetic (P = .0002). This same group, however, has significantly longer injection times (P < .0001). Pain during the injection process or during surgery was not different between the two groups. Conclusions. This RCT comparing traditional and microprocessor controlled methods of administering local anaesthetic showed similar levels of discomfort in both groups. While the microprocessor-controlled group used less volume, the total time for the administration was significantly greater.
PMCID: PMC3197004  PMID: 22110923
21.  The prevalence and nature of cardiac arrhythmias in horses following general anaesthesia and surgery 
The prevalence and nature of arrhythmias in horses following general anaesthesia and surgery is poorly documented. It has been proposed that horses undergoing emergency surgery for gastrointestinal disorders may be at particular risk of developing arrhythmias. Our primary objective was to determine the prevalence and nature of arrhythmias in horses following anaesthesia in a clinical setting and to establish if there was a difference in the prevalence of arrhythmias between horses with and without gastrointestinal disease undergoing surgery. Our secondary objective was to assess selected available risk factors for association with the development of arrhythmias following anaesthesia and surgery.
Horses with evidence of gastrointestinal disease undergoing an exploratory laparotomy and horses with no evidence of gastrointestinal disease undergoing orthopaedic surgery between September 2009 and January 2011 were recruited prospectively. A telemetric electrocardiogram (ECG) was fitted to each horse following recovery from anaesthesia and left in place for 24 hours. Selected electrolytes were measured before, during and after surgery and data was extracted from clinical records for analysis. Recorded ECGs were analysed and the arrhythmias characterised. Multivariable logistic regression was used to identify risk factors associated with the development of arrhythmias.
Sixty-seven horses with gastrointestinal disease and 37 without gastrointestinal disease were recruited. Arrhythmias were very common during the post-operative period in both groups of horses. Supra-ventricular and bradyarrhythmias predominated in both groups. There were no significant differences in prevalence of any type of arrhythmias between the horses with or without gastrointestinal disease. Post-operative tachycardia and sodium derangements were associated with the development of any type of arrhythmia.
This is the first study to report the prevalence of arrhythmias in horses during the post-operative period in a clinical setting. This study shows that arrhythmias are very common in horses following surgery. It showed no differences between those horses with or without gastrointestinal disease. Arrhythmias occurring in horses during the post-anaesthetic period require further investigation.
PMCID: PMC3269988  PMID: 22112936
equine; post-anaesthetic; electrocardiography; arrhythmia
22.  A Comparative Study of Induction, Maintenance and Recovery Characteristics of Sevoflurane and Halothane Anaesthesia in Pediatric Patients (6 months to 6 years) 
Patients & Methods:
In a randomized , double blind clinical study, we studied 30 children, aged 6 months to 6 years, to compare halothane and sevoflurane anaesthesia in patients undergoing short surgical procedures under general anaesthesia. All the patients were premedicated with atropine 0.02mg kg-1and midazolam 0.1mg kg-1body weight intravenously and received inhalation induction using nitrous oxide in oxygen supplemented with either halothane (maximum inspired concentration of 5%) or sevoflurane (maximum inspired concentration of 8%). Induction was by inhalation of increasing concentrations of sevoflurane (1%) or halothane (0.5%) in the vaporizing setting after every three breaths of the patient.
Time to loss of eyelash reflex and tracheal intubation was more rapid using sevoflurane. Cardiac arrhythmias were significantly more frequent during halothane than sevoflurane anaesthesia. Psychomotor recovery was more rapid after sevoflurane anaesthesia. Children who received sevoflurane had comparatively less nausea and vomiting and the incidence of clinically important side effects was significantly less with sevoflurane anaesthesia.
We conclude that induction with sevoflurane in nitrous oxide and oxygen leads to fast loss of consciousness and provides ideal conditions for managing the airway without supplemental opioids or muscle relaxants with haemodynamic stability and is therefore a reasonable alternative to halothane for paediatric patients.
PMCID: PMC3087258  PMID: 21547175
Halothane; Sevoflurane; paediatric; children
23.  Local anaesthesia for pain control during outpatient hysteroscopy: systematic review and meta-analysis 
Objective To compare the effects of different types of local anaesthetic for pain control during outpatient hysteroscopy.
Design Systematic review and meta-analysis of randomised controlled trials.
Setting Outpatient hysteroscopy clinics.
Participants Women undergoing diagnostic or operative hysteroscopy as outpatients—that is, without general anaesthesia.
Study selection criteria Medline, Embase, CINAHL, the Cochrane library, and reference lists of relevant studies. Two reviewers independently selected trials. Data were abstracted on quality, characteristics, and results.
Results There were 20 trials (2851 participants). Data from 15 of these were meta-analysed in subgroups defined by type of intervention and study quality. Intracervical (standardised mean difference −0.36, 95% confidence interval −0.61 to −0.10, I2=0%) and paracervical (−1.28, −2.22 to −0.35, I2=97%) injections of local anaesthetic significantly reduced the pain in women undergoing hysteroscopy as outpatients, whereas transcervical (−0.11, −0.31 to 0.10, I2=27%) and topical application (−0.32, −0.97 to 0.33, I2= 90%) did not. Meta-regression showed that paracervical injection was superior to the other anaesthetic methods (P=0.04), a finding that was supported by the high quality subgroup of studies. Use of local anaesthetic did not have a significant effect on the incidence of vasovagal episodes (P=0.09).
Conclusions Paracervical local anaesthetic injection is the best method of pain control for women undergoing hysteroscopy as outpatients.
PMCID: PMC2844502  PMID: 20332307
24.  Safety of general anaesthesia and surgery in acute hepatic porphyria. 
Gut  1994;35(8):1112-1115.
Patients with acute hepatic porphyria are denied essential operations because of concern that general anaesthesia and surgery will precipitate a life threatening porphyric crisis. This study assessed the safety of surgery under general anaesthesia in these patients. A combined prospective and retrospective case note study, with a biochemical study, was conducted in 25 patients with acute hepatic porphyria undergoing 38 surgical operations. Clinical outcome measures were survival and occurrence of porphyric crisis after surgery. The biochemical activity of porphyria was assessed by measurement of the perioperative 24 hour excretion of the haem precursors delta amino-laevulinic acid (ALA) and porphobilinogen (PBG). There were no deaths or crises after 29 operations in 19 patients who were known to have porphyria before their surgery, and therefore given only appropriate drugs. These operations include such major procedures as mitral valve replacement, hip replacement, coronary artery grafting, cholecystectomies, and renal transplantation. In eight of these patients the urinary excretion of ALA and PBG were studied, and showed no sustained postoperative increase. Nine operations were performed in eight patients before the diagnosis of porphyria was known and who thus received routine anaesthetic agents. Seven of these patients developed a postoperative porphyric crisis. Two of them died. It is concluded therefore that even the most major surgery can be undertaken safely in patients with porphyria. The risk is for undiagnosed cases.
PMCID: PMC1375065  PMID: 7926916
25.  Genotoxicity, cytotoxicity and gene expression in patients undergoing elective surgery under isoflurane anaesthesia 
Mutagenesis  2011;26(3):415-420.
There are numerous studies reporting on the effects of inhalation anaesthesia in cells of exposed individuals but not much is known about the ability of isoflurane (ISF) to induce oxidative DNA damage. However, surgery is often associated with a temporary perioperative immunological alteration, and some volatile anaesthetics seem to contribute to a transient lymphocytopenia after surgery. We conducted a study to evaluate a possible genotoxic effect, including oxidative DNA damage, and apoptosis in peripheral lymphocytes of 20 patients American Society of Anaesthesiologists physical status I undergoing minor elective surgery lasting at least 120 min, under anaesthesia with ISF. We also investigated the expression of several genes in blood cells. Blood samples were collected at three time points: before anaesthesia (T1), 2 h after the beginning of anaesthesia (T2) and on the first post-operative day (T3). General DNA damage and oxidised bases (Fpg and endo III-sites) in blood lymphocytes were evaluated using the comet assay. Lymphocytes were phenotyped and apoptosis was evaluated by flow cytometry. In addition, expressions of hOGG1 and XRCC1, genes involved in DNA repair, and BCL2, a gene related to apoptosis, were assessed by quantitative real-time polymerase chain reaction. Results showed no statistically significant difference in the level of DNA damage and oxidised bases among the three sampling times. Anaesthesia with ISF did not increase the percentage of cells in early or late apoptosis in cytotoxic or helper T lymphocytes. Lower hOGG1 and BCL2 expressions were detected at T3 in comparison to the other two previous time points, and there was significantly lower expression of XRCC1 at T3 in relation to T2. In conclusion, the exposure to ISF did not result in genotoxicity and cytotoxicity in lymphocytes and in toxicogenomic effect in leukocytes, although DNA repair and apoptosis-related genes were down-regulated on the first post-operative day.
PMCID: PMC3081333  PMID: 21257718

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